Question

Chloroformates have the functional group \(\mathrm{R}-\mathrm{O} \mathrm{Cl}\), in which \(\mathrm{R}\) is often a tert-butyl or benzyl group. A chloroformate is used in the following synthesis of the antibacterial drug linezolid (Zyvox). CC(=O)NCC1CN(c2ccc(N3CCOCC3)c(F)c2)C(=O)O1 Based on your knowledge of carboxylic acid derivatives, predict the product of the following transformation used in a synthesis of linezolid (Zyvox). The new functional group created is called a carbamate. Carbamates are often used as protecting groups for amine groups during complex syntheses.

Short answer

Answer: The product of the transformation is a carbamate-protected amine present in the final linezolid compound with the structure \(\mathrm{R}-\mathrm{N}(\mathrm{H})\mathrm{COOR'}\), where R' is a tert-butyl or benzyl group. The new functional group created in this reaction is a carbamate.

Step-by-step solution

Identify the functional groups in the chloroformate and the reactant amine

In this exercise, we are given a chloroformate with the functional group \(\mathrm{R}-\mathrm{O} \mathrm{Cl}\), and we know that R is a tert-butyl or benzyl group. Additionally, we are given a reactant amine found in the linezolid molecule. Our goal is to determine the product of the reaction between these two groups.

Understand the mechanism of the reaction between chloroformate and amine

The reaction between a chloroformate and an amine is a nucleophilic acyl substitution, where the nucleophile is the nitrogen atom in the amine group, and the electrophile is the carbonyl carbon in the chloroformate. The reaction proceeds as follows: 1. The nitrogen atom in the amine group attacks the carbonyl carbon in the chloroformate, forming a tetrahedral intermediate. 2. The tetrahedral intermediate collapses, leading to the expulsion of the chloride ion as a leaving group. 3. A carbamate functional group is formed in the final product, with the structure \(\mathrm{R}-\mathrm{N}(\mathrm{H})\mathrm{COOR'}\).

Determine the structure of the final product

Following the mechanism from Step 2, we can determine the structure of the final product. The nucleophilic amine nitrogen is connected to the carbonyl carbon of the chloroformate group, forming a carbamate functional group. The remaining groups in the reactant amine and the chloroformate stay intact. The final product of the reaction between the amine found in linezolid (Zyvox) and the chloroformate is a carbamate-protected amine present in the final linezolid compound: CC(=O)NCC1CN(c2ccc(N3CCOCC3)c(F)c2)C(=O)OR', with R' being the tert-butyl or benzyl group